Rheumatoid arthritis (RA) and osteoarthritis (OA) and their treatments may affect patients' quality of life not only by their effects on the musculosketal system, but also by collateral effects on other organ systems. Morbidity and mortality from cardiovascular diseases may be increased by physical inactivity, systemic inflammation and possibly by treatment with corticosteroids, methotrexate, or non-steroidal anti- inflammatory drugs (NSAIDs) selective of cyclooxygenase-2. Use of NSAIDs may decrease the risk of colorectal cancer, while use of immunosuppressive medications may increase the hematological malignancies. This project proposes a series of cohort studies based on longitudinal data on approximately 3500 patients with RA and 2500 patients with OA that will: 1) define the risks of morbidity and mortality from acute myocardial infarction and stroke among patients with RA and OA; 2) determine the relative contributions of systemic inflammation, musculoskeletal morbidity, and medications to the risk of myocardial infarction and stroke; 3) define the risks of morbidity and mortality from colorectal cancer among patients with RA and OA; 4) determine the contribution of NSAID use to the risk of colorectal cancer in these patients; 5) define the risks of morbidity and mortality form hematologic malignancies among patients with RA; and 6) determine the contribution of immunosuppressive medications and anti-cytokine drugs to the risk of hematologic malignancies. Knowledge of the reciprocal relationship between chronic arthritis and comorbid conditions will provide a more complete understanding of the health consequences of RA and OA, identify risk factors for comorbid conditions, suggest strategies for intervention, and more fully characterize the long-term consequences of treatment. Medication choices may therefore be made with more precise information. Many of the most important outcomes of arthritis and it treatments may come from their indirect effects on other chronic illnesses.